Paclitaxel Compared With Doxorubicin in Treating Patients With Advanced AIDS-Related Kaposi's Sarcoma

National Cancer Institute (NCI)

Status and phase: Completed; Phase 3

Conditions: AIDS-related Kaposi Sarcoma

Treatments: Procedure: quality-of-life assessment; Drug: pegylated liposomal doxorubicin hydrochloride; Drug: paclitaxel; Other: laboratory biomarker analysis

Study type: Interventional

Funder types: NIH

Identifiers

NCT00003350

E1D96

CDR0000066331 (Registry Identifier)

NCI-2012-03149

U10CA021115 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Randomized phase III trial to compare the effectiveness of paclitaxel with that of doxorubicin in treating patients who have advanced AIDS-related Kaposi's sarcoma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether paclitaxel is more effective than doxorubicin in treating patients with advanced AIDS-related Kaposi's sarcoma

Full description

PRIMARY OBJECTIVES:

I. To compare the effect of therapy with paclitaxel to therapy with liposomal doxorubicin on progression-free survival and on global assessment of quality of life of subjects with advanced AIDS-related K.S.

II. To compare the toxicity profile of intravenous paclitaxel with liposomal doxorubicin in patients with advanced AIDS-related K.S.

III. To compare the overall and complete response rate of intravenous paclitaxel with liposomal doxorubicin in patients with advanced AIDS-related K.S.

IV. To evaluate the effect of intravenous paclitaxel as compared with therapy with liposomal doxorubicin on the clinical course of HIV infection in patients with advanced AIDS-related K.S., by monitoring CD4 and CD8 lymphocyte subsets, HIV viral load and the incidence and type of opportunistic infections.

V. To explore the relationship between viral load and response to the therapy for patients with AIDS-related K.S.

VI. To describe the relationship between "technical" response as measured by the current KS response criteria and the clinical benefit of therapy as measured by the revised KS clinical benefit criteria.

OUTLINE: This is a randomized study. Patients are randomized to receive either paclitaxel (arm I) or doxorubicin HCL liposome(arm II).

Arm I: Patients receive paclitaxel over 3 hours by intravenous infusion. Treatment course repeats every 2 weeks. Patients are evaluated every third course.

Arm II: Patients receive doxorubicin HCL liposome over 30-60 minutes by intravenous infusion. Treatment course is repeated every 3 weeks. Patients are evaluated before every odd course.

Patients in both arms continue treatment if there is no disease progression or unacceptable toxicity. Patients with complete response continue on study treatment for 2 courses beyond documented complete response.

Quality of life is assessed before, during, and after treatment.

Patients are followed every 3 months for the first 2 years, then every 6 months for years 2-5, and then annually thereafter.

PROJECTED ACCRUAL: There will be 240 patients (120 patients in each arm) accrued into this study over 24 months.

Enrollment: 240 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Serologic diagnosis of HIV infection as documented by a positive ELISA and confirmed with a western blot, other federally approved HIV diagnostic test, or HIV viral load measurement

• Biopsy-proven, measurable Kaposi's sarcoma with any of the following:

  • Progressive cutaneous disease
  • Symptomatic oropharyngeal or conjunctival lesions
  • Any visceral involvement
  • Tumor-related lymphedema
  • Tumor-related ulceration or pain
  • NOTE: All patients must have measurable disease; baseline measurements must be obtained < 4 weeks prior to registration

• ECOG performance status 0-2

• ANC >= 1000/mm³ (with or without the use of colony-stimulating factors)

• Platelet count >= 50,000/mm³

• Hemoglobin >= 8 gm/dL

• Bilirubin < 1.5 x the upper limit of normal (unless elevation is due to Crixivan administration with isolated elevation in conjugated bilirubin)

• SGOT or SGPT =< 5 x the upper limit of normal

• Creatinine =< 2.1 mg/dl

• Women must not be pregnant or lactating due to potential toxicity of therapy

• Women of childbearing potential and sexually active men must be advised to use an accepted and effective method of contraception due to potential toxicity of therapy

• No prior systemic cytotoxic chemotherapy for Kaposi's sarcoma

• Prior radiation therapy must have been discontinued >= 7 days prior to randomization and must NOT have been delivered to marker lesions; (NOTE: Radiation therapy will not be permitted during study treatment)

• No active, untreated infection (no new opportunistic infectious complications within the previous week requiring a change in antibiotics); maintenance therapy for opportunistic infections will be allowed

• No prior or concomitant malignancy other than curatively treated carcinoma in situ of the cervix or basal/squamous cell carcinoma of the skin

• No neuropsychiatric history or altered mental status that might prevent informed consent or affect the ability of the patient to comply with the study

• Institutions must ask patients to participate in the quality of life portion of the protocol; however, patients may decline participation in this component of the study and still be eligible; the reason for refusal or inability to complete the QOL assessments must be documented in the Assessment Compliance Form (#596)

• Must not be known to be sensitive to E. coli derived proteins

• No history of cardiac insufficiency (NY Heart Association status >= 2)

• Patients must be on stable (no change in drugs or doses) antiretroviral therapy for greater than 14 days prior to study; a combination regimen is required; ideally this will be a protease inhibitor containing triple therapy regimen

• Patients must give signed, written informed consent

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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240 participants in 2 patient groups

Arm I (paclitaxel)

Experimental group

Description:

Patients receive paclitaxel over 3 hours by intravenous infusion. Treatment course repeats every 2 weeks. Patients are evaluated every third course. Patients in both arms continue treatment if there is no disease progression or unacceptable toxicity. Patients with complete response continue on study treatment for 2 courses beyond documented complete response. Quality of life is assessed before, during, and after treatment.

Treatment:

Other: laboratory biomarker analysis

Drug: paclitaxel

Procedure: quality-of-life assessment

Arm II (pegylated liposomal doxorubicin hydrochloride)

Experimental group

Description:

Patients receive doxorubicin HCL liposome over 30-60 minutes by intravenous infusion. Treatment course is repeated every 3 weeks. Patients are evaluated before every odd course. Patients in both arms continue treatment if there is no disease progression or unacceptable toxicity. Patients with complete response continue on study treatment for 2 courses beyond documented complete response. Quality of life is assessed before, during, and after treatment.

Treatment:

Other: laboratory biomarker analysis

Procedure: quality-of-life assessment

Drug: pegylated liposomal doxorubicin hydrochloride